title: Effect of oral insulin on diabetes-induced intestinal mucosal growth in rats.
abstract: BACKGROUND
  To evaluate the intestinal response to the induction of diabetes and to oral insulin (OI) administration in a rat.
  
  
  METHODS
  Male Sprague-Dawley rats were divided into four experimental groups: control rats, CONTR-INS rats that were treated with OI given in drinking water for 7 days, diabetic rats that were injected with one dose of streptozotocin, and diabetic rats treated with OI. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis, bax and bcl-2 mRNA and protein levels, insulin receptor expression and ERK protein levels were determined at sacrifice. A one-way ANOVA for comparison, followed by Tukey's test for pair-wise comparison, were used for statistical analysis.
  
  
  RESULTS
  Induction of diabetes resulted in a significant increase in bowel and mucosal weight (P < 0.05), mucosal protein (P < 0.05), villus height and crypt depth in jejunum and ileum (P < 0.05), and mucosal DNA in ileum (P < 0.05) (vs. control animals). Diabetes also enhances ERK-induced cell proliferation (P < 0.05) and concomitant bax/bcl-2 induced cell apoptosis (P < 0.05). Treatment of diabetic rats with OI resulted in a significant decrease in jejunal protein content (P < 0.05), jejunal and ileal villus height (P < 0.05), and jejunal crypt depth (P < 0.05), as well as an inhibition of ERK-related cell proliferation in ileum (P < 0.05). Expression of insulin receptor was down-regulated following OI administration in both control and diabetic animals.
  
  
  CONCLUSIONS
  Experimental STZ-induced diabetes causes intestinal mucosal growth and enhances enterocyte turnover in a rat model. OI administration diminishes diabetes-accelerated cell turnover and diabetes-induced mucosal hyperplasia.
authors.affiliation: Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. igor-dr@internet-zahav.net
authors.forename: Igor
authors.initials: I
authors.lastname: Sukhotnik
authors.forename: Raanan
authors.initials: R
authors.lastname: Shamir
authors.forename: Yulia
authors.initials: Y
authors.lastname: Bashenko
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Mogilner
authors.forename: Elena
authors.initials: E
authors.lastname: Chemodanov
authors.forename: Ron
authors.initials: R
authors.lastname: Shaoul
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Coran
authors.forename: Naim
authors.initials: N
authors.lastname: Shehadeh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000378:metabolism; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology*; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D008055:Lipids / Q000097:blood; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015431:Weight Loss; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D002097:C-Reactive Protein; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt